Sodium hydride → HCID 22860775, compound

HRID 363121Notes

Reaction equation

HRID 363121 reaction equation
[H-].[Na+].[CH2:3]([N:10]1[CH2:15][CH2:14][O:13][C@H:12]([OH:16])[C@H:11]1[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[F:23][C:24]([F:38])([F:37])[C:25]1[CH:26]=[C:27]([CH:30]=[C:31]([C:33]([F:36])([F:35])[F:34])[CH:32]=1)[CH2:28]Br.C([O-])(O)=O.[Na+]>C1COCC1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH2:3]([N:10]1[CH2:15][CH2:14][O:13][C@H:12]([O:16][CH2:28][C:27]2[CH:30]=[C:31]([C:33]([F:35])([F:36])[F:34])[CH:32]=[C:25]([C:24]([F:23])([F:37])[F:38])[CH:26]=2)[C@H:11]1[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 1225733,5-Bis(trifluoromethyl)benzyl bromideHCID 516892Sodium BicarbonateHCID 22860777HCID 22860777, compound

Product 1

HCID 22860775HCID 22860775, compoundYield 59.1%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 0.592 g (14.8 mmol) of NaH in 30 mL of dry THF at 0° C. was added 3.32 g (12.3 mmol) of 4-benzyl-2-(S)-hydroxy-3-(R)-phenyl-morpholine prepared in step A. After 15 min 0.915 g of tetrabutylammonium iodide (2.47 mmol) and 2.4 mL (13 mmol) of 3,5-bis(trifluoromethyl)benzyl bromide were added. The resulting mixture was stirred at ice-bath temperature for 1 h, then poured into saturated NaHCO3 solution and extracted with ethyl acetate (EtOAc). The organic layers were combined, washed with brine, dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was chromatographed on a Waters Prep500 HPLC system using 50% EtOAc/Hexane to isolate 3.6 g (59%) of 4-Benzyl-2-(S)-(3,5-bis(trifluoromethyl)benzyloxy)-3-(R)-phenylmorpholine.

Workup

  1. extractionextracted with ethyl acetate (EtOAc)
  2. washwashed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuo
  6. customthe residue was chromatographed on a Waters Prep500 HPLC system

Sources & evidence

ORD record
ord-2207e39f1ec145ab9ddf97014472c4bc
Source dataset
uspto-grants-1999_02
Patent number
US05872116

Reaction notes

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